tbuckley/cabot-search huggingface dataset:
Socioeconomic factors associated with stages of bladder cancer at diagnosis: Analysis of the National Cancer Database.
Authors: Alexandra Taylor, Jillian Marie Gallegos, Kiana Verplancke, Kevin McMahon, Peter T. Silberstein, Mary Elizabeth Dahl
Journal: Journal of Clinical Oncology (2022)

e16531 Background: The average 5-year survival rate of Bladder Cancer (BC) in the US is 77%, yet the 5-year survival for BC with metastatic disease is 5%. The extreme differences in survival rate based on stage and metastasis highlight the importance of determining the social factors at the time of diagnosis. The objective of this study is to identify the socioeconomic and demographic factors associated with receiving a delayed bladder cancer diagnosis (stage IV) vs an early (stage 0-I) diagnosis. Methods: Using the National Cancer Database, this study analyzed 511,177 patients diagnosed with stage 0-I and stage IV BC between 2004 and 2018. Patients were analyzed based on race, sex, insurance type, Charlson-Deyo comorbidity score, level of education, income, geographic location, and education. Socioeconomic factors of patients were analyzed using multivariate analysis, chi square analysis, and one-way ANOVA. Results: Significant (P &lt; 0.05) associations were identified between certain socioeconomic factors and presentation of bladder cancer at an advanced stage (stage IV). African Americans were 66% more likely to be diagnosed with stage IV diagnosis compared to Caucasians (p &lt; .001 and 95% CI = 1.598-1.724). Hispanics were 22% more likely than non-Hispanics to present with a stage IV diagnosis (p &lt; .001 and 95% CI = 1.114-1.327). Females were 34% more likely than men to present with stage IV diagnosis (p &lt; .001 and 95% CI = 1.307-1.367). Patients with private insurance were 53% less likely to be diagnosed with a stage IV diagnosis than those who were uninsured (p &lt; .001 and 95% CI = 0.448-0.509). Patients with one or more co-morbidities (Charleson-Deyo score ≥1) were more likely to present with a stage IV diagnosis than those with no co-morbidities (p &lt; .001). Patients whose median household income was ≥ $63,000 were 33% less likely to present with a stage IV diagnosis than those whose median household income was &lt; $63,000 (p &lt; .031). Conclusions: Factors associated with increased likelihood of bladder cancer presentation at advanced stage compared to early stage include race, ethnicity, sex, insurance status, one or more co-morbidities, and a median household income under $63,000.
Upfront Modified Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan Plus Panitumumab Versus Fluorouracil, Leucovorin, and Oxaliplatin Plus Panitumumab for Patients With <i>RAS/BRAF</i> Wild-Type Metastatic Colorectal Cancer: The Phase III TRIPLETE Study by GONO
Authors: Daniele Rossini, Carlotta Antoniotti, Sara Lonardi, Filippo Pietrantonio, Roberto Moretto, Lorenzo Antonuzzo, Alessandra Boccaccino, Federica Morano, Marco Brugia, Carmelo Pozzo, Federica Marmorino, Francesca Bergamo, Emiliano Tamburini, Alessandro Passardi, Giovanni Randon, Sabina Murgioni, Beatrice Borelli, Angela Buonadonna, Mirella Giordano, Gabriella Fontanini, Veronica Conca, Vincenzo Formica, Massimo Aglietta, Roberto Bordonaro, Giuseppe Aprile, Gianluca Masi, Luca Boni, Chiara Cremolini
Journal: Journal of Clinical Oncology (2022)

To verify whether the intensification of the upfront chemotherapy backbone with a modified schedule of modified fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFOXIRI) increases the activity of fluorouracil, leucovorin, and oxaliplatin when both regimens are combined with panitumumab as initial treatment for RAS and BRAF wild-type (wt) metastatic colorectal cancer (mCRC).TRIPLETE was a prospective, open-label, phase III trial in which previously untreated patients with unresectable RAS and BRAF wt mCRC were randomly assigned 1:1 to modified FOLFOX/panitumumab (control group) or mFOLFOXIRI/panitumumab (experimental group) up to 12 cycles, followed by fluorouracil/-leucovorin/panitumumab until disease progression. The primary end point was objective response rate (ORR) according to RECIST 1.1. Hypothesizing an ORR of 60% in the control group, 432 cases provided 90% power to a two-sided chi-square test for heterogeneity with a two-sided alpha error of .05 to detect ≥ 15% differences between arms (ClinicalTrials.gov identifier: NCT03231722).From September 2017 to September 2021, 435 patients were enrolled (control group/experimental group: 217/218) in 57 Italian sites. One hundred sixty (73%) patients treated with mFOLFOXIRI plus panitumumab and 165 (76%) patients treated with modified FOLFOX plus panitumumab achieved RECIST response (odds ratio 0.87, 95% CI, 0.56 to 1.34, P = .526). No differences in early tumor shrinkage rate (57%/58%, P = .878) and deepness of response (median: 48%/47%, P = .845) were reported, nor in R0 resection rate (25%/29%, P = .317). No significant difference between arms was reported in terms of progression-free survival (median progression-free survival: 12.7 in the experimental group v 12.3 months in the control group, hazard ratio: 0.88, 95% CI, 0.70 to 1.11, P = .277).The intensification of the upfront chemotherapy backbone in combination with panitumumab does not provide additional benefit in terms of treatment activity at the price of increased gastrointestinal toxicity in patients with RAS and BRAF wt mCRC.
Assessing the immunomodulatory effect of testosterone on outcomes of patients with advanced solid tumors treated with immunotherapy using the National Cancer Database.
Authors: Thejus Jayakrishnan, Wei Wei, Laura Sena, Pradnya Dinkar Patil
Journal: Journal of Clinical Oncology (2022)

e18805 Background: Androgens have been described to suppress immune responses to various benign and pathogenic antigens, accounting in part for sex-based differences in incidence and severity of autoimmunity, infection, and malignancy. We hypothesized that testosterone exposure alters immune tolerance to solid tumors and outcomes to cancer immunotherapy. In an attempt to isolate the effect of testosterone exposure on outcomes to treatment with immunotherapy, we utilized age as a surrogate for testosterone level and sought to test whether younger men with higher testosterone would have different outcomes following immunotherapy than older men with lower testosterone, relative to women. Methods: National Cancer Database (NCDB) was queried for patients with advanced non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), or melanoma, who received immunotherapy as first-line systemic treatment. These patients were divided by quartiles for age (Q1 (youngest) through Q4 (oldest)) and a Multivariate Cox proportional hazard model was used to test the interaction between sex and age on survival outcomes for each cancer type while adjusting for the Charlson-Deyo comorbidity index. Results: The study included 23,741 NSCLC (median age 66 years, interquartile range (IQR) 59 – 74), 1741 RCC (62 y, IQR 55 – 69), and 5825 melanoma (64 y, IQR 54 - 73) patients. The majority of patients were male – 52.3%, 71.3%, and 68.2% for each cancer type respectively. The median overall survival (OS) following first-line immunotherapy declined with increasing age in each cancer type (Q1 &gt; Q4). No significant interaction between age group and sex for any of the cancer types was identified (table). Notably, male patients in any group and cancer type did not have statistically longer OS following immunotherapy than female patients. Conclusions: This study did not show that age altered sex-based differences in outcomes to immunotherapy in patients with advanced solid tumors. It is possible that age is a poor surrogate for testosterone level in this patient population, that additional confounding factors were present, or that testosterone exposure does not modify outcomes to immunotherapy. Future studies will directly correlate serum testosterone levels with outcomes to immunotherapy in patients with advanced cancer.[Table: see text]
Pharmaceutical industry payments to physicians for the promotion of cancer drugs.
Authors: Aaron Philip Mitchell, Akriti Mishra Meza, Niti U. Trivedi, Peter Brian Bach, Mithat Gonen
Journal: Journal of Clinical Oncology (2022)

1580 Background: Personal financial payments from the pharmaceutical industry to oncologists are common and increasing. A prevalent view is that the purpose of industry payments to physicians is to facilitate education on new drugs. However, little is known regarding the distribution and trends in industry payments related to cancer drugs. The goal of this study was to characterize current patterns in industry payments related to cancer drugs, and test whether these patterns are consistent with an educational purpose. Methods: We included on-patent cancer drugs without generic/biosimilar competitors, and used publicly-available federal data sources to measure Medicare spending (proxy for overall drug revenue), number of prescribers, and industry payments (Open Payments, which includes data regarding which the drug[s] was the subject of each payment) for each calendar year from 2014-2018. We analyzed General Payments to individual physicians, which encompasses payment types such as meals, travel, consulting, and speaking fees. We tested two hypotheses implied by the claim that industry payments serve educational purposes. First, payment amounts should not be associated with drug revenue. To test this hypothesis, we used generalized estimating equations (GEE) to model the association between mean per-physician industry payments and Medicare spending. Second, payments related to a given drug should decline over time as physicians become educated. To test this hypothesis, we determined the relative year-to-year change in industry payments for all cases wherein consecutive years were observed, and used GEE to estimate the year-to-year change with respect to duration of time since initial FDA approval. Results: The sample included 89 drugs and 361 drug-year observations. The total amount of industry payments for oncology drugs increased during the study period, from $53,333,854 in 2014 to $90,343,731 in 2018. There was no association between log-transformed mean, per-physician industry payments and per-physician Medicare spending (estimate -0.001, 95%CI: -0.005, 0.004). In aggregate, Industry payments for cancer drugs were greatest immediately after FDA approval and trended downward over time; the estimated industry payments in the subsequent year for a drug with mean payments of $1,000 per-physician in the index year was: $681* for drugs 0-4 years since approval, $825 for drugs 5-9 years, and $679* for drugs≥10 years (*p&lt;0.05). Conclusions: The absence of association between industry payments and Medicare spending and the decline in industry payments for drug subsequent to approval are consistent with claims that these payments function to facilitate physician education.
Phase II Trial of Adjuvant Nivolumab Following Salvage Resection in Patients with Recurrent Squamous Cell Carcinoma of the Head and Neck
Authors: Jennifer L. Leddon, Shuchi Gulati, Sulsal Haque, Casey Allen, Sarah Palackdharry, Maria Mathews, Nicky Kurtzweil, Muhammed Kashif Riaz, Vinita Takiar, Misako Nagasaka, Yash Patil, Chad Zender, Alice Tang, Brian Cervenka, Julie McGrath, W. Michael Korn, Benjamin H. Hinrichs, Roman Jandarov, Nusrat Harun, Ammar Sukari, Trisha M. Wise-Draper
Journal: Clinical Cancer Research (2022)

Locoregional relapse in patients with head and neck squamous cell carcinoma (HNSCC) is common, approaching 50% for some subsites despite multimodality therapy. Salvage surgery is the standard of care, but able to achieve durable control in only a minority of patients. While adjuvant radiotherapy or chemo-radiotherapy is offered to select patients, this approach can be prohibitively toxic. Given the activity and tolerability of programmed death-1 inhibitors in metastatic HNSCC, we investigated the safety and efficacy of adjuvant nivolumab after salvage surgical resection.This was an open-label, multi-institutional phase II clinical trial (NCT03355560). Patients with recurrent, resectable HNSCC were enrolled within 6 weeks of salvage surgery. Six 28-day cycles of adjuvant nivolumab were planned. The primary endpoint was 2-year disease-free survival (DFS) more than 58%, based on an institutional historical control group of 71 patients with recurrent HNSCC who underwent salvage surgery.Between February 2018 and February 2020, 39 patients were enrolled. At a median follow-up of 22.1 months, 2-year DFS was 71.4% [95% confidence interval (CI), 57.8-88.1] and the 2-year overall survival (OS) was 73% (95% CI, 58-91.8). Three of 39 (8%) patients experienced grade 3 treatment-related adverse events and 3 of 39 (8%) discontinued treatment due to side effects. Ten of 39 had locoregional recurrence, while 2 of 10 also had synchronous metastatic disease. There was no difference in DFS between PD ligand-1 (PD-L1)-positive and PD-L1-negative patients. There was a nonsignificant trend toward improved DFS in patients with high tumor mutational burden (P = 0.083).Adjuvant nivolumab after salvage surgery in locally recurrent HNSCC is well tolerated and showed improved DFS compared with historical controls.
Adjuvant immunotherapy in patients with high-risk muscle-invasive urothelial carcinoma and the potential impact of informative censoring
Authors: A. Martini, D. Raggi, H. Joshi, G. Fallara, L. Nocera, F. Belladelli, F. Montorsi, A. Necchi, M.D. Galsky
Journal: European Urology (2022)
Outcomes of the BRCA quality improvement dissemination program in three health systems.
Authors: Erica M. Bednar, Minxing Chen, Michael T. Walsh, Amanda L. Eppolito, Kelly B. Teed, Molly H. Klein, Han Chao, Jordan Berg, Erin Bowman, Cara S. Yobbi, Rebekah C. Krukenberg, Sandra Jenkinson, Jennifer Moore, Cassie Garcia, Timothy Goedde, Nichole A. Morman, Elizabeth C. Bowdish, Emaline Wise, Kellie S. Rath, Karen H. Lu
Journal: Journal of Clinical Oncology (2022)

10603 Background: The BRCA Quality Improvement Dissemination Program (BQIDP) was disseminated to 3 community-based health systems’ oncology clinics in 2017. The BQIDP occurred over 3 years and aimed to increase rates of guideline-recommended referral (ref), genetic counseling (GC), and germline genetic testing (GT) for patients diagnosed with invasive epithelial ovarian, fallopian tube, and primary peritoneal cancer (OC) and triple-negative breast cancer diagnosed at age 60 or younger (TNBC). The BQIDP applied virtual implementation facilitation to support sites’ development, implementation, and tracking of quality improvement (QI) interventions. Interventions were adapted from prior QI initiatives and published interventions. Methods: Baseline metrics (patients diagnosed 1/1/2015 to site’s BQIDP launch date Autumn 2017) were compared to metrics of patients diagnosed during BQIDP implementation (site launch dates Autumn 2017 to Autumn 2020). Two-sample test of proportions was used to assess for statistically significant change in rates pre and post BQIDP implementation at each site. QI interventions targeted provider and patient education, retrospective and prospective case finding with alerts to providers and patients, case finding by review of somatic test results and genetic counselor tumor board attendance, streamlined ref and scheduling processes, and infusion-suite based GC. Results: All clinics increased rates compared to baseline (Table). Statistically significant improvement was noted for patients with OC in receipt of GC at Site A, ref and receipt of GC at site B, and receipt of GC at site C. Statistically significant improvement was noted for patients with TNBC in ref and GT at sites A and B. Conclusions: Improved rates of ref, GC and GT for patients with OC and TNBC were observed at all 3 sites compared to baseline. Baseline ref, GC, and GT metrics for patients with TNBC were higher than for patients with OC at all sites. Tailored and facilitated QI efforts can promote patients’ receipt of guideline-recommended cancer genetics services in health system oncology clinics. [Table: see text]
PD-L1 is overexpressed on tumorspheres cultured from circulating cancer stem cells in patients with breast cancer.
Authors: Monika Pizon, Dorothea Schott, Ulrich A. Pachmann, Marek Pizon, Katharina Pachmann
Journal: Journal of Clinical Oncology (2022)

3052 Background: Circulating cancer cells, and in particular their very rare subpopulation, circulating cancer stem cells (cCSCs), are responsible for recurrence and metastasis. The exact role of cCSCs in escape of cancer from immunosurveillance is still unknown, but recent studies revealed that enhanced PDL-1 expression in cancer stem cells is linked to immune evasion and could crucially contribute to the maintenance of CSC self-renewal. Understanding the mechanisms behind this PDL-1 overexpression in cancer stem cells is critical for developing more effective anti-PD-1/PD-L1 therapy. Therefore the aim of the study was to determine the number of tumorspheres and expression of PD-L1 on tumorspheres cultured from cCSC in breast cancer patients. Methods: 110 patients with breast cancer in different stages of disease were included in this study. The determination of circulating cancer stem cells was performed using the sphere-forming assay. Additionally anti-PDL-1 antibody staining was applied to examine PDL-1 expression on breast tumorspheres. Results: We have developed an innovative in vitro platform for detection of cCSCs from peripheral blood of cancer patients. The number of tumorspheres increased significantly with tumor progression and aggressiveness of primary tumor. Patients with metastatic disease had statistically more tumorspheres as compared to patients without metastasis (30 vs 10/100µl blood, p &lt; 0.05). Patients with multiple metastasis had more tumorspheres compared to patients with single metastases (60 vs 30/100µl blood, p &lt; 0.05). The number of tumorspheres was positively correlated with Ki-67, Her2 status and grade score in primary breast tumors. We observed high PDL-1 expression and their considerable heterogeneity in enriched tumorspheres. Conclusions: The number of tumorspheres cultured from peripheral blood directly reflects aggressiveness and proliferation capacity of primary tumor. The presence of tumorspheres with expression of PDL-1 might suggest their immunregulatory potential. Better understanding of the interaction between cCSCs and tumor immunology may help to identify strategies to eradicate the minor subpopulation that escapes conventional therapy attack, thus providing a solution to the problem of drug resistance and metastasis.
Clinical impact of the changes of muscle volume during various systemic therapies in patients with unresectable hepatocellular carcinoma.
Authors: Hiroaki Matsumoto, Kaoru Tsuchiya, Yuka Hayakawa, Yuki Tanaka, Shun Ishido, Kento Inada, Sakura Kirino, Koji Yamashita, Tsubasa Nobusawa, Tatsuya Kakegawa, Mayu Higuchi, Kenta Takaura, Shohei Tanaka, Chiaki Maeyashiki, Shun Kaneko, Nobuharu Tamaki, Yutaka Yasui, Hiroyuki Nakanishi, Masayuki Kurosaki, Namiki Izumi
Journal: Journal of Clinical Oncology (2022)

e16177 Background: Sarcopenia is associated with clinical outcomes in cirrhosis and hepatocellular carcinoma (HCC). However, the clinical impact of muscle volume during systemic therapy is unknown. We investigated the changes in muscle volume during various systemic therapies for HCC. Methods: The patients with unresectable HCC (u-HCC) treated with a molecular targeted agent as initial systemic therapy were included. The skeletal muscle mass index (SMI) was calculated from the skeletal muscle area at the L3 level of the lumbar vertebrae using computed tomography. Sarcopenia was defined as an L3 SMI value≦42 cm 2 /m 2 for men and 38 cm 2 /m 2 for women. ΔSMI was defined as the difference between baseline and 6-14 weeks after the administration of the agent. Results: A total of 174 patients was analyzed. The 1 st -line agent was sorafenib (SOR) (n = 89), lenvatinib (LEN)(n = 58), and atezolizumab plus bevacizumab (ATE+BEV) (n = 27). In three groups, ATE+BEV group had significantly fewer discontinuation due to adverse events. (ATE+BEV 6 cases, LEN 31 cases, SOR 32 cases, p = 0.014). The median PFS was 4.1, 3.0, and 6.1 months in SOR, LEN, and ATE+BEV. The median Δ In patients treated with ATE+BEV, pretreatment sarcopenia was not associated with OS and PFS, while the patients with a SMI decrease (at 6-14W, n = 12) had significantly shorter PFS than the patients without a SMI decrease (n = 15) (p = 0.026). The best radiological response based on RECIST ver1.1 in ATE+BEV was CR (n = 2), PR(n = 6), SD(n = 15), and PD (n = 3). The patients without a SMI decrease tended to have better disease control rate than patients with a SMI decrease (100% vs. 75%, p = 0.08). There were no significant differences in age, etiology, ALBI score, BCLC stage, and pretreatment AFP between the patients with and without a SMI decrease. The significant factor associated with PFS after the administration of ATE+BEV as 1 st -line was a decrease of SMI (HR9.44, 95% CI 1.04-85.6, p = 0.046). In patients treated with SOR and LEN, pretreatment sarcopenia and SMI decrease were not significantly associated with OS and PFS. Conclusions: The decrease of muscle volume at 6-14W was significantly associated with PFS in patients treated with ATE+BEV, while pretreatment sarcopenia was not a significant factor. Monitoring muscle volume during immunotherapy would be useful in clinical practice.
Use and correlates of carotid ultrasound in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.
Authors: Yolanda C Bryce, Gregory T. Armstrong, Wendy M. Leisenring, Jillian Whitton, Eric Jessen Chow, Brent R. Weil, Bryan Dieffenbach, Rebecca M. Howell, Kevin C. Oeffinger, Paul C. Nathan, Emily S. Tonorezos
Journal: Journal of Clinical Oncology (2022)

e22023 Background: Survivors of childhood cancer with history of radiation therapy (RT) to the head/neck/chest are at increased risk for stroke. Children’s Oncology Group Guidelines recommend carotid ultrasound (CU) when clinically indicated or 10 years after RT ≥ 40Gy to the neck. Yet, the use of CU has not been previously described. Methods: 8,693 survivors of childhood cancer (median age at diagnosis 8.0 years, range 0-20; median age at evaluation 37.4, range 18-65) diagnosed between 1970-1999 were asked if they had ever had a CU. Cardiovascular disease (CVD) was defined as any of the following: stroke, congestive heart failure, hypertension, myocardial infarction, coronary heart disease, or arrythmia. Prevalence ratios (PR) were calculated; age and sex-adjusted multivariable Poisson regression models evaluated factors associated with CU. Results: 4.9% (427) of survivors had a history of stroke and 28% (2,442) had a history of any CVD. Of these, 40.0% (171) with a history of stroke and 28.6% (748) with any CVD had CU. Comparatively, 14.6% (1,404) without a stroke and 11.1% (798) without any CVD had a CU (both p&lt;0.0001 vs those with condition). Among survivors without CVD, having seen only a primary care physician was not associated with CU (PR 0.84 95% CI 0.58-1.25, p = 0.36), while seeing a cancer specialist (+/- a primary care physician) (PR 1.83 95% CI 1.23-2.79, p = 0.036) was associated with increased likelihood of CU compared to seeing neither. Survivors who had had other surveillance studies, including a colonoscopy (PR 1.76 95% CI 1.44-2.17, p&lt;0.0001), skin cancer exam (PR 1.62 95% CI 1.30-2.03, p=0.0002), or mammogram (PR 2.06 95%CI 1.42-3.07, p&lt;0.0001) were more likely to have a carotid ultrasound, compared to those without that test. Having a history of anthracyclines or RT to the neck were associated with higher prevalence of CU, with RT to the neck exhibiting a dose-response relationship (Table). Conclusions: CU was more common among survivors with a history of stroke or other CVD event. In those without CVD, CU use was associated with anthracyclines and RT dose exposures and with care provided by a cancer specialist. A high proportion (70%) of survivors who received &gt;40Gy RT to the neck have never had a CU, suggesting that greater awareness of guidelines is needed.[Table: see text]